Investigators from Memorial Sloan Kettering Cancer Center have reported more encouraging news about one of the most exciting methods of cancer treatment today. The largest clinical study ever conducted to date of patients with advanced leukemia found that 88 percent achieved complete remissions after being treated with genetically modified versions of their own immune cells. The results were published today in Science Translational Medicine.

“These extraordinary results demonstrate that celltherapy is a powerful treatment for patients who have exhausted all conventional therapies,” said Michel Sadelain, MD, PhD, Director of the Center for Cell Engineering at Memorial Sloan Kettering and one of the study’s senior authors. “Our initial findings have held up in a larger cohort of patients, and we are already looking at new clinical studies to advance this novel therapeutic approach in fighting cancer.”

Adult B cellacutelymphoblasticleukemia (B-ALL), a type of blood cancer that develops in B cells, is difficult to treat because the majority of patients relapse. Patients with relapsed B-ALL have few treatment options; only 30 percent respond to salvage chemotherapy. Without a successful bone marrow transplant, few have any hope of long-term survival.

In the current study, 16 patients with relapsed B-ALL were given an infusion of their own genetically modified immune cells, called T cells. The cells were “reeducated” to recognize and destroy cancer cells that contain the protein CD19. While the overall complete response rate for all patients was 88 percent, even those with detectable disease prior to treatment had a complete response rate of 78 percent, far exceeding the complete response rate of salvage chemotherapy alone.

Dennis J. Billy, C.Ss.R, of Wynnewood, Pennsylvania, was one of the first patients to receive this treatment more than two years ago. He was able to successfully undergo a bone marrow transplant and has been cancer-free and back at work teaching theology since 2011. Paolo Cavalli, a restaurant owner from Oxford, Connecticut, remains in complete remission eight months after receiving his personalized T cell treatment.

A History of Scientific Achievements for Cell-Based Therapies

Cell-based, targeted immunotherapy is a new approach to treating cancer that harnesses the body’s own immune system to attack and kill cancerous cells. Unlike with a common virus such as the flu, our immune system does not recognize cancer cells as foreign and is therefore at a disadvantage in eradicating the disease. For more than a decade, researchers at Memorial Sloan Kettering have been exploring ways to reengineer the body’s own T cells to recognize and attack cancer. In 2003, they were the first to report that T cells engineered to recognize the protein CD19, which is found on B cells, could be used to treat B cell cancers in mice.

“Memorial Sloan Kettering was the first center to report successful outcomes using this CD19-targeted approach in B-ALL patients,” said Renier Brentjens, MD, PhD, Director of Cellular Therapeutics at Memorial Sloan Kettering and one of the study’s senior authors. “It’s extremely gratifying to witness the astonishing results firsthand in my patients, having worked for more than a decade developing this technology from the ground up.”

In March 2013, the same team of researchers first reported the results of five patients with advanced B-ALL who were treated with cell therapy. Remarkably, all five patients achieved complete remissions.

Results Demonstrate Potential of New Therapy

In the current study, seven of the 16 patients (44 percent) were able to successfully undergo bone marrow transplantation — the standard of care and the only curative option for B-ALL patients — following treatment. Three patients were ineligible due to failure to achieve a complete remission, three were ineligible due to preexisting medical conditions, two declined, and one is still being evaluated for a potential bone marrow transplant. Historically, only 5 percent of patients with relapsed B-ALL have been able to transition to bone marrow transplantation.

The study also provides guidelines for managing side effects of cell therapy, which can include severe flu-like symptoms such as fever, muscle pain, low blood pressure, and difficulty breathing, referred to as cytokine release syndrome. The researchers developed diagnostic criteria and a laboratory test that can identify which patients are at greater risk for developing this syndrome.

Additional studies to determine whether cell therapy can be applied to other types of cancer are already underway, and studies to test whether B-ALL patients would benefit from receiving targeted immunotherapy as frontline treatment are being planned.

This research was supported by the Terry Fox Foundation, the American Society of Hematology-Amos Medical Faculty Development Program, the Alliance for Cancer Gene Therapy, the Carson Family Fund, the Major Family Fund for Cancer Research, Joel and Yvette Nallah, the Lewis Sanders Fund, the Damon Runyon Cancer Research Foundation, Kate’s Team, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Cancer Foundation for Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering.

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acute (uh-KYOOT)

Symptoms or signs that begin and worsen quickly; not chronic.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

B cell (… sel)

A type of immune cell that makes proteins called antibodies, which bind to microorganisms and other foreign substances, and help fight infections. A B cell is a type of white blood cell. Also called B lymphocyte.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

blood (blud)

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

blood pressure (blud PREH-sher)

The force of circulating blood on the walls of the arteries. Blood pressure is taken using two measurements: systolic (measured when the heart beats, when blood pressure is at its highest) and diastolic (measured between heart beats, when blood pressure is at its lowest). Blood pressure is written with the systolic blood pressure first, followed by the diastolic blood pressure (for example 120/80).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

bone marrow (bone MAYR-oh)

The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

bone marrow transplantation (bone MAYR-oh tranz-plan-TAY-shun)

A procedure to replace bone marrow that has been destroyed by treatment with high doses of anticancer drugs or radiation. Transplantation may be autologous (an individual's own marrow saved before treatment), allogeneic (marrow donated by someone else), or syngeneic (marrow donated by an identical twin).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cell (sel)

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

chemotherapy (KEE-moh-THAYR-uh-pee)

Treatment with drugs that kill cancer cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

clinical (KLIH-nih-kul)

Having to do with the examination and treatment of patients.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cohort (KOH-hort)

A group of individuals who share a common trait, such as birth year. In medicine, a cohort is a group that is part of a clinical trial or study and is observed over a period of time.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

complete remission (kum-PLEET reh-MIH-shun)

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete response.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

complete response (kum-PLEET reh-SPONTS)

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cytokine (SY-toh-kine)

A substance that is made by cells of the immune system. Some cytokines can boost the immune response and others can suppress it. Cytokines can also be made in the laboratory by recombinant DNA technology and used in the treatment of various diseases, including cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

fever (FEE-ver)

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

foreign (FOR-in)

In medicine, foreign describes something that comes from outside the body. A foreign substance in the body’s tissues, such as a bacterium or virus, may be recognized by the immune system as not belonging to the body. This causes an immune response. Other foreign substances in the body, such as artificial joints, are designed to not cause an immune response.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

immune system (ih-MYOON SIS-tem)

The complex group of organs and cells that defends the body against infections and other diseases.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

immunotherapy (IH-myoo-noh-THAYR-uh-pee)

Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in immunotherapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biological therapy, biotherapy, and BRM therapy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

infusion (in-FYOO-zhun)

A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

laboratory test (LA-bruh-tor-ee...)

A medical procedure that involves testing a sample of blood, urine, or other substance from the body. Tests can help determine a diagnosis, plan treatment, check to see if treatment is working, or monitor the disease over time.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

leukemia (loo-KEE-mee-uh)

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

lymphoblastic (LIM-foh-BLAS-tik)

Refers to lymphoblasts (a type of immature white blood cell).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

protein (PROH-teen)

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

relapse (REE-laps)

The return of a disease or the signs and symptoms of a disease after a period of improvement.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

remission (reh-MIH-shun)

A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

response (reh-SPONTS)

In medicine, an improvement related to treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

response rate (reh-SPONTS...)

The percentage of patients whose cancer shrinks or disappears after treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

standard of care (STAN-durd ... kayr)

Treatment that experts agree is appropriate, accepted, and widely used. Also called best practice, standard medical care, and standard therapy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

syndrome (SIN-drome)

A set of symptoms or conditions that occur together and suggest the presence of a certain disease or an increased chance of developing the disease.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

T cell (... sel)

A type of immune cell that can attack foreign cells, cancer cells, and cells infected with a virus. T cells can also help control immune responses. A T cell is a type of white blood cell. Also called T lymphocyte and thymocyte.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

therapeutic (THAYR-uh-PYOO-tik)

Having to do with treating disease and helping healing take place.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

therapy (THAYR-uh-pee)

Treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

transplantation (tranz-plan-TAY-shun)

A surgical procedure in which tissue or an organ is transferred from one area of a person’s body to another area, or from one person (the donor) to another person (the recipient).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

virus (VY-rus)

In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)